PROJECT SUMMARY Brain injury in the preterm infant is a problem of enormous magnitude and is mediated largely by cerebrovascular mechanisms emanating from disturbed vasoregulation in the immature brain. Pressure passivity is a major manifestation of disturbed cerebral vasoregulation and is pivotal in both hypoxic-ischemic (HI) and hemorrhagic brain injury in premature infants. Cerebral pressure passivity develops when systemic blood pressure (BP) is unstable and cerebral pressure autoregulation is impaired. We have demonstrated that hypotension, as well as fluctuations in blood pressure and cerebral pressure passivity are common in sick premature infants. The lack of an integrated bedside technique that continuously monitors the dynamic relationship between these signals to identify cerebral pressure-passivity has impeded the formulation of rational strategies for BP management aimed at preventing brain injury in the preterm infant. We have developed such a system that measures continuous cerebral near infrared spectroscopy (NIRS) and BP changes to identify periods of cerebral pressure passivity at the bedside of sick infants. We measure the coherence (using transfer function analysis) between changes in systemic BP and the cerebral NIRS hemoglobin difference (HbD) signal; we then derive a pressure-passive index (PPI) in order to quantify pressure passivity over time. In the research proposed here, we aim to begin validating the ability of cerebral pressure passivity measured by our technique to identify imminent germinal matrix-intraventricular hemorrhage (GM-IVH) detected by 4-hourly `scout' US studies. In addition, we will seek to define characteristics of systemic BP and CO2 levels that predispose to pressure passivity. If validated, this approach will have enormous benefit for the advance of biomedical and clinical research and most importantly will lead to the eventual development of rational brain-oriented hemodynamic management that prevents the devastating brain injuries of prematurity. As such the work proposed here is squarely directed at maximizing opportunities for this extremely vulnerable population to fulfill their potential for a healthy and productive life unhampered by disease or disability.